Association Studies Between ST2Gene Polymorphism And Severity Of Coronary Artery Disease

Part Association Studies between ST2gene polymorphism and myocardial infarction in Chinese han nationalityObjective:Coronary heart disease (CHD) is a complex chronic disease caused by multiple genetic and environmental factors. The gene plays an important role in the pathogenesis of CHD and it has been proved that ST2gene polymorphism is associated with CHD. The level of serum sST2in patients with AMI rises, which may be affected by ST2gene polymorphism at the gene level. In this study, a case-control study method was performed to investigate the relationship between ST2gene polymorphism and acute myocardial infarction (AMI). We also analyzed the level of serum sST2among different genotypes in positive loci to investigate the effects of genotype on the sST2levelsMethod:Using Sequenom Mass Array genotyping technique, we performed a case-control association analysis on a total of161individuals with acute myocardial infarction and297normal controls (NC) via tag SNPs in the genes encoding ST2. We selected tag SNPs according to Haploview (v.4.2) based on Hap Map CHB data(v.3, release2) and based on the previous studies about coronary heart disease (CAD). So,12SNPs were selected to perform the study. To further investigate the effects of genotype on the sST2levels, the level of serum of sST2from a cohort of46patients with AMI and59normal controls were measured when they were admitted to hospital.Result:The frequencies of rs10515922genotypes of TT, CT, CC were80.7%,16.8%,2.5%in MI group and72.4%,25.6%,2.0%in NC group, which showed significant difference between two groups. However, the allele frequencies of C and T in rs10515922were10.9%,89.1%in MI group and14.8%,85.2%in NC group, which had no significant difference between the two groups. Binary Logistic regression analysis shows that patients with genotype CT (OR=0.588, P=0.033,95%CI-0.360-0.959) and combined genotype CC+CT (OR=0.625, P=0.049,95%CI=0.392-0.997) both had a lower risk for suffering from AMI when compared to patients with genotype TT. Multiple factor Logistic regression analysis also showed that rs10515922was significantly associated with the incidence of MI after age, gender, smoking, hypertension, BMI and diabetes mellitus were adjusted, and people with CC genotype have lower risk of suffering from AMI(OR=0.348, P=0.037,95%CI=0.129-0.936), however, the CC+CT genotype in rs10515922had no significantly associated with the incidence of MI after adjustment with logistic regression analysis. Comparing the levels of serum sST2between among different genotypes showed that the serum sST2concentrations of genotype CC-.CT-.TT in the first day were2.54+0.97ng/ml,2.71±1.47ng/ml,2.77±1.99ng/ml respectively in AMI group, which had no significant difference among them (F=0.024, p=0.976)Conclusion:rs1055922in ST2gene may be involved in the development of acute myocardial infarction. Patients with genotype CC+CT or CT had lower risk for suffering from AMI than those with genotype TT. The genotypes in rs10515922had no significant association with the level of serum sST2, which indicates that the level of serum sST2in patients with AMI may be not affected by the ST2gene polymorphism from gene level. Part Ⅱ Association Studies between ST2gene polymorphism and angiographic severity of coronary artery disease Objective:Gene plays an important role in the pathogenesis of CHD and we have proved that ST2gene polymorphism is associated with myocardial infarction. In this study, a case-control study method was performed to investigate the relationship between ST2gene polymorphism and angiographic severity of CAD. coronary artery angiography was used to determine the number of involved blood vessels.Method:Using Sequenom Mass Array genotyping technique, we performed an angiography-based case-controled study consisting of352individuals with coronary heart disease (193myocardial infarction and159no-myocardial infarction) to investigate the association between the selected polymorphisms of ST2gene and angiographic severity of CAD via tag SNPs in the genes encoding ST2. We selected tag SNPs according to Haploview (v.4.2) based on Hap Map CHB data(v.3, release2) and based on the previous studies about coronary heart disease (CAD).Result:9SNPs that had allele frequencies grater than0.05were selected to perform the study. The distribution frequencies of rs12999364genotype CC, CT, TT in ST2gene were33.3%,52.9%,13.7%in single lesion group and45.7%,37.7%,16.6%in multivessel lesion group, which showed significant difference between two groups (p=0.016). And the distribution frequency of combined genotype TT+CT was lower in multivessel lesion group than in single lesion group (66.7%vs54.3%, p=0.021), which also showed significant difference between two groups. Further analysis performed by binary Logistic regression showed that patients with genotype CT (OR=0.519, P=0.006,95%CI=0.326-0.826) and combined genotye (TT+CT)(OR=0.593, P=0.019,95%CI=0.383-0.918) had lower risk for suffering from multivessel lesion when compared to patients with genotype CC. With adjustment for traditional danger factors (age, gender, smoking, drinking, hypertension, diabetes mellitus, the CAD history of family, BMI, triglyceride and total cholesterol), multiple factor logistic regression analysis showed that genotype CT and TT+CT in rs12999364, were independent protective factors for multi-vessel lession in the coronary artery disease (CAD) people(CT:OR=0.471,P=0.003,95%CI=0.285-0.778; TT+CT: OR=0.555, P=0.014,95%CI-0.347-0.888)Conclusion:ST2gene polymorphism rs12999364was significantly associated with angiographic severity of coronary heart disease. Patients with genotyer TT and TT+CT had lower risk for suffering from multiplevessel lesion in coronary artery disease.